One-year investigator-blind randomized multicenter trial comparing asacol 2.4 g once daily with 800 mg three times daily for maintenance of remission in ulcerative colitis

Abstract

BackgroundMesalazine (Asacol) is still widely prescribed in divided doses for ulcerative colitis (UC), despite evidence that adherence is improved by once-daily (OD) prescribing. We aimed to investigate whether OD Asacol was as effective as three times (TDS) daily dosing, and to evaluate the role of treatment adherence.MethodsAn investigator-blind randomized trial was undertaken comparing OD Asacol (three 800 mg tablets) versus one 800 mg TDS in maintenance of remission of UC over 1 year. The primary endpoint was relapse rate, and noninferiority would be concluded if the lower limit of the two-sided 95% confidence interval (CI) of the difference in proportions relapsing (TDS-OD) exceeded −10%. Adherence was measured by tablet counts and self-reported adherence. A subgroup of patients used a bottle cap that recorded all bottle opening events.ResultsIn all, 213 patients were randomized. In the intention-to-treat (ITT) population, relapse rates were 31% (95% CI 22%–40%) in the OD and 45% (95% CI 35%–54%) in the TDS group. Primary analysis confirmed the noninferiority of OD dosing. Two of the study populations, ITT and per-protocol (PP), showed potential superiority of OD dosing. All measures of adherence showed that it was significantly better in the OD group. Multivariate analysis, however, showed OD dosing was associated with lower relapse risk independently of adherence.ConclusionsOD dosing with Asacol 2.4 g is as safe and effective as TDS dosing, and secondary analysis confirmed significantly reduced relapse rates. The benefit, however, was clinically borderline and may relate in part to ease of adherence. (Inflamm Bowel Dis 2012)

Challenges in the Diagnosis and Management of Inflammatory Bowel Disease in the Elderly

“…Patients with at least four prescriptions have even lower adherence rates [30]. Single dosing formulations decrease the pill burden and improve compliance [31,32]. Practical difficulties can impair the routine use of topical therapy.…”

Can oral 5-aminosalicylic acid be administered once daily in the treatment of mild-to-moderate ulcerative colitis? A meta-analysis of randomized-controlled trials

“…Our search strategy initially yielded 1763 citations. Of these, we included nine unique studies in this meta-analysis [8,14,15,17,18,[20][21][22][23]. Table 1 shows the characteristics of the studies included.…”

“…Table 1 shows the characteristics of the studies included. Three trials were comparing a once daily dosing regime with a divided (twice or thrice daily) dosing regime of oral delayed-release mesalamine for induction of remission in UC [8,14,17], and six trials were comparing a once daily dosing regime with a divided (twice or thrice daily) dosing of oral delayed-release mesalamine for maintenance of remission in UC [15,18,[20][21][22][23]. The severity of UC was considered to be mild to moderate in all trials.…”

“…Research results have demonstrated that oral delayedrelease mesalamine can be administered once daily [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. However, there is no meta-analysis to evaluate the pooled efficacy and safety of a once-daily regime of oral mesalamine.…”

Unmet Medical Needs in Ulcerative Colitis: An Expert Group Consensus

“…Moreover, long-term clinical study data in over 2,800 IBD patients who were treated for up to 5 years demonstrate that this drug has a favourable safety profile with no increased risk of serious or opportunistic infections or malignancy versus placebo [52]. Head-to-head comparative studies of vedolizumab versus TNF inhibitors are needed [53].Adherence to UC treatments, including 5-ASA, is often poor and non-adherence is associated with enhanced risk of relapse [54]. 5-ASA and azathioprine seem to have particularly poor rates of adherence, with patients on these drugs missing 45 and 25%, respectively, of their total prescribed doses -mostly involuntarily due to forgetfulness [55].…”